Diethyl Succinate

(1; R = Et)

[123-25-1]  · C8H14O4  · Diethyl Succinate  · (MW 174.20) (2; R = Me)

[106-65-0]  · C6H10O4  · Dimethyl Succinate  · (MW 146.14) (3; = R = i-Pr)

[924-88-9]  · C10H18O4  · Diisopropyl Succinate  · (MW 202.25) (4; R = (-)-menthyl)

[34212-59-4]  · C24H42O4  · Dimenthyl Succinate  · (MW 394.59)

(acyloin condensation,1 self-condensation,2 Stobbe condensation,3 and various enolate reactions)

Physical Data: (1): mp 18-19 °C; bp 217.7 °C; d 1.047 g cm-3. (2): mp -20 °C; bp 200 °C; d 1.117 g cm-3. (3): bp 247 °C; d 0.99 g cm-3. (4): mp 62-64 °C; bp 200-205 °C/2 mmHg.

Solubility: sol H2O (19.2 g L-1 at 20 °C).

Acyloin Condensation.1

A simplification and improvement of the acyloin condensation of diethyl succinate (1) to give 1,2-bis(trimethylsilyloxy)cyclobutene has been reported (eq 1).4

Self-Condensation.

Diethyl 2,5-dioxo-1,4-cyclohexanedicarboxylate can be prepared by the self-condensation of (1) in the presence of a strong base catalyst (eq 2).2

Stobbe Condensation.3

The succinates react with ketones (eq 3)5 or aldehydes (eq 4)6 in the presence of Sodium Hydride or alkoxides to form monoesters of a-alkylidene succinic acids. The Stobbe condensation products are important synthetic intermediates which have been used in the preparation of various natural products such as lignan isolariciresinol, cordigerine, and hinokinin.7

Metal enolates of (1) also react with various esters (eqs 5 and 6).8,9

Diethyl Dilithiosuccinate.

This reagent (5) is readily prepared10 by treatment of (1) with Lithium Diisopropylamide (2 equiv) at -78 °C in THF (eq 7). The dianion can be isolated and trapped to give the bis-silylated product (eq 8).10 Interestingly, using only 1 equiv of LDA also gave the same compound as the major product (45%) together with unreacted (1) (30%) and only a small amount of the monosilylated product (5%), suggesting that the di-enolate (5) is preferentially formed in the reaction.

g-Butyrolactone Synthesis.

The di-enolate (5) reacts with aldehydes and ketones (eq 9)11 and a-keto esters (eq 10)12 to give g-butyrolactones in good yields. These types of lactones are useful intermediates in the synthesis of cyclopentenones.13

Alkylation.

The dianion (5) can be mono- or dialkylated with reactive halides in good yields in the presence of Hexamethylphosphoric Triamide.10,11 Successive alkylation of (5) with Benzyl Bromide and Iodomethane gave the mixed alkylated product in 60% yield (eq 11).10

Carbocyclization.

Alkylation of the dianion (6) with dihalides provides a facile method for the preparation of carbocycles.14 The reaction has been successfully applied to the synthesis of a natural propellane, modhephene (eq 12).15

An efficient asymmetric carbocyclization to give three- to six-membered ring compounds can be achieved using the dianion of chiral dimenthyl succinate (8) (eq 13).16

Direct condensation of dianion (7) with 2-(bromomethyl)acrylate provides a one-pot preparation of cyclopentanones (eq 14).17 The use of the diisopropyl ester in this reaction is superior to diethyl or dibenzyl derivatives, both of which gave lower yields of the coupling products.

Related Reagents.

N-Chlorosuccinimide; 2,5-Dihydro-2,5-dimethoxyfuran; 2,5-Dimethoxytetrahydrofuran; Succindialdehyde; Succinic Anhydride; Succinimide.


1. (a) Bloomfield, J. J.; Owsley, D. C.; Nelke, J. M. OR 1976, 23, 259. (b) Bloomfield, J. J.; Nelke, J. M. OSC 1988, 6, 167. (c) Rühlmann, K. S 1971, 236.
2. Nielson, A. T.; Carpenter, W. R. OSC 1973, 5, 288.
3. (a) Johnson, W. S.; Daub, G. H. OR 1951, 6, 1. (b) House, H. O. Modern Synthetic Reactions; Benjamin: Menlo Park, CA; 1972; pp 663-666.
4. Fadel, A.; Canet, J.-L; Salaün, J. SL 1990, 89.
5. Johnson, W. S.; Schneider, W. P. OSC 1963, 4, 132.
6. Brown, E.; Daugan, A. H 1987, 26, 1169.
7. Bambagiotti-Alberti, M.; Coran, S. A.; Vincieri, F. F.; Mulinacci, N.; Pieraccini, G. M. L. H 1988, 27, 2185.
8. (a) Jones, G.; Jones, R. K. JCS(P1) 1973, 26. (b) Kelly, T. R.; Ohashi, N.; Armstrong-Chong, R. J.; Bell, S. H. JACS 1986, 108, 7100.
9. (a) Bottorff, E. M.; Moore, L. L. OSC 1973, 5, 687. (b) Dean, F. H.; Pattison, F. L. M. CJC 1963, 41, 1833.
10. Long, N. R.; Rathke, M. W. SC 1981, 11, 687.
11. Pohmakotr, M.; Reutrakul, V.; Phongpradit, T.; Chansri, A. CL 1982, 687.
12. Reutrakul, V.; Kusamran, K.; Wattanasin, S. H 1977, 6, 715.
13. Eaton, P. E.; Carlson, G. R.; Lee, J. T. JOC 1973, 38, 4071.
14. Wilkening, D.; Mundy, B. P. SC 1984, 14, 227.
15. Mundy, B. P.; Wilkening, D.; Lipkowitz, K. B. JOC 1985, 50, 5727.
16. (a) Misumi, A.; Iwanaga, K.; Furuta, K.; Yamamoto, H. JACS 1985, 107, 3343. (b) Iwanaga, K.; Furuta, K.; Yamamoto, H. OS 1989, 67, 76.
17. Furuta, K.; Misumi, A.; Mori, A.; Ikeda, N.; Yamamoto, H. TL 1984, 25, 669.

Sompong Wattanasin

Sandoz Research Institute, East Hanover, NJ, USA



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